Methods for stereospecific synthesis of polyene aldehydes

Abstract

Methods for stereospecific synthesis of 9-cis olefins and retinoids. In one particular aspect, a cis olefin is generated via a lactol ring opening with complete retention of double bond configuration.

We claim: 
     
       1. A method for producing a cis-olefin, comprising: combining a lactol of the formula ##STR6## with acid and solvent reactants; heating said reactants; and   quenching and separating the predominant resulting aldehyde product having the formula ##STR7## wherein R 1  represents a lower or branched alkyl having 1-12 carbons, or phenyl, and can be methyl only if R 2  is a hydrogen or a lower alkyl having 1-8 carbons,   R 2  represents hydrogen, a lower alkyl having 1-8 carbons, or halogen,   or R 1  and R 2  taken together form a phenyl, cyclohexyl, or cyclopentyl ring,   R 3  represents a lower alkyl having 1-8 carbons, polyene compounds of the formula R 1  --CH═CH--C(R 1 )═CH--(E or Z orientation), cycloalkyl, or aryl, and   R 5  represents hydrogen, a lower alkyl having 1-8 carbons, or halogen.   
     
     
       2. The method of claim 1 wherein R 1  is methyl, R 2  is hydrogen, R 3  is 2,6,6-trimethylcyclohexen-1-yl, and R 5  is hydrogen. 
     
     
       3. The method of claim 1 wherein said acid is selected from the group consisting of para-toluene sulfonic acid, pyridinium hydrochloride trichloro- or trifluoro-acetic acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, oxalyic acid, and hydrochloric acid. 
     
     
       4. The method of claim 1 wherein said solvent is selected from the group consisting of chlorinated solvents, apolar solvents, and coordinating solvents.